NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells - PubMed (original) (raw)
doi: 10.1038/ni1325. Epub 2006 Apr 2.
Affiliations
- PMID: 16582911
- DOI: 10.1038/ni1325
NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells
Jadee L Upshaw et al. Nat Immunol. 2006 May.
Abstract
NKG2D is an important immunosurveillance receptor that responds to stress-induced ligand expression on tumors and virus-infected cells. Human natural killer cells express NKG2D and require the transmembrane adaptor DAP10 to initiate their full cytotoxic activation. However, DAP10 has no immunoreceptor tyrosine-based activation motif and thus the mechanism of recruiting 'downstream' effector proteins is unclear. We show here that binding of the p85 subunit of phosphatidylinositol-3- kinase to DAP10 could not by itself trigger cell-mediated cytotoxicity and that binding of an intermediate consisting of the DAP10 binding partner Grb2 and the effector molecule Vav1 (Grb2-Vav1) to DAP10 was sufficient to initiate tyrosine-phosphorylation events. For full calcium release and cytotoxicity to occur, both Grb2-Vav1 and p85 had to bind to DAP10. These findings identify a previously unknown mechanism by which NKG2D-DAP10 mediates cytotoxicity and provides a framework for evaluating activation by other receptor complexes that lack immunoreceptor tyrosine-based activation motifs.
Similar articles
- Phosphatidylinositol 3-kinase activation is required to form the NKG2D immunological synapse.
Giurisato E, Cella M, Takai T, Kurosaki T, Feng Y, Longmore GD, Colonna M, Shaw AS. Giurisato E, et al. Mol Cell Biol. 2007 Dec;27(24):8583-99. doi: 10.1128/MCB.01477-07. Epub 2007 Oct 8. Mol Cell Biol. 2007. PMID: 17923698 Free PMC article. - NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway.
Billadeau DD, Upshaw JL, Schoon RA, Dick CJ, Leibson PJ. Billadeau DD, et al. Nat Immunol. 2003 Jun;4(6):557-64. doi: 10.1038/ni929. Epub 2003 May 11. Nat Immunol. 2003. PMID: 12740575 - Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and microtubule dynamics.
Graham DB, Cella M, Giurisato E, Fujikawa K, Miletic AV, Kloeppel T, Brim K, Takai T, Shaw AS, Colonna M, Swat W. Graham DB, et al. J Immunol. 2006 Aug 15;177(4):2349-55. doi: 10.4049/jimmunol.177.4.2349. J Immunol. 2006. PMID: 16887996 - NKG2D-mediated activation of cytotoxic lymphocytes: unique signaling pathways and distinct functional outcomes.
Upshaw JL, Leibson PJ. Upshaw JL, et al. Semin Immunol. 2006 Jun;18(3):167-75. doi: 10.1016/j.smim.2006.03.001. Epub 2006 May 24. Semin Immunol. 2006. PMID: 16723257 Review. - Human natural killer lymphocytes through the engagement of natural cytotoxicity receptors and NKG2D can trigger self-aggression.
Poggi A, Zocchi MR. Poggi A, et al. Autoimmun Rev. 2007 Apr;6(5):295-9. doi: 10.1016/j.autrev.2006.07.003. Epub 2006 Aug 4. Autoimmun Rev. 2007. PMID: 17412301 Review.
Cited by
- Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior cytolytic activity.
van Vliet AA, van den Hout MGCN, Steenmans D, Duru AD, Georgoudaki AM, de Gruijl TD, van IJcken WFJ, Spanholtz J, Raimo M. van Vliet AA, et al. Mol Ther Oncol. 2024 Sep 2;32(4):200870. doi: 10.1016/j.omton.2024.200870. eCollection 2024 Dec 19. Mol Ther Oncol. 2024. PMID: 39346765 Free PMC article. - Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.
Mohammad Taheri M, Javan F, Poudineh M, Athari SS. Mohammad Taheri M, et al. J Transl Med. 2024 Aug 5;22(1):736. doi: 10.1186/s12967-024-05534-8. J Transl Med. 2024. PMID: 39103889 Free PMC article. Review. - NK Receptors Replace CD28 As the Dominant Source of Signal 2 for Cognate Recognition of Cancer Cells by TAA-specific Effector CD8+ T Cells.
Dong B, Obermajer N, Tsuji T, Matsuzaki J, Bonura C, Withers H, Long M, Chavel C, Olejniczak SH, Minderman H, Edwards RP, Storkus WJ, Romero P, Kalinski P. Dong B, et al. Res Sq [Preprint]. 2023 Oct 19:rs.3.rs-3399211. doi: 10.21203/rs.3.rs-3399211/v1. Res Sq. 2023. PMID: 37886562 Free PMC article. Preprint. - The Role and Regulation of the NKG2D/NKG2D Ligand System in Cancer.
Tan G, Spillane KM, Maher J. Tan G, et al. Biology (Basel). 2023 Aug 2;12(8):1079. doi: 10.3390/biology12081079. Biology (Basel). 2023. PMID: 37626965 Free PMC article. Review. - Fluid shear stress enhances natural killer cell's cytotoxicity toward circulating tumor cells through NKG2D-mediated mechanosensing.
Hu B, Xin Y, Hu G, Li K, Tan Y. Hu B, et al. APL Bioeng. 2023 Aug 11;7(3):036108. doi: 10.1063/5.0156628. eCollection 2023 Sep. APL Bioeng. 2023. PMID: 37575881 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous